Our library of drug research abstracts drawn from the medical literature is updated on a regular schedule, and you can be assured that new clonidine research articles will be listed here shortly after becoming available to us.
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Medical research on clonidine
Methods Find Exp Clin Pharmacol. 2008 Apr; 30(3): 193-9
Lazahari MI, Sattar MA, Abdullah NA, Khan MA, Johns EJ
This study examined the sympathoinhibitory effects of clonidine and a novel clonidine analog, AL-12, in rat models of genetic hypertension and a combined state of genetic hypertension and diabetes. Rats in the treatment groups were given either clonidine or AL-12 while the respective control groups received either saline or Tween 80 for 6 days. Physiological data were collected during this period, which was followed by acute studies on day 7 when bolus administrations (i.v.) of graded doses of noradrenaline, phenylephrine and methoxamine were carried out. It was observed that in AL-12-treated nondiabetic spontaneously hypertensive rats (SHR), the pressure responses to all adrenergic agonists were greater (p < 0.05) in the treated group, while in the diabetic SHR rats a larger pressure response was observed only to noradrenaline (p < 0.05). In nondiabetic SHR rats treated with clonidine, a greater (p < 0.05) pressure response was observed only in the case of phenylephrine. In the diabetic SHR rats treated with clonidine, the pressure responses to the adrenergic agonists were similar (p > 0.05) in the treated and its control animals except that methoxamine caused a greater (p < 0.05) pressure response in the control group. The data obtained suggest that clonidine and AL-12 act possibly via vascular alpha1 and alpha2 adrenoceptors present at both pre- and postsynaptic locations.
Eur J Pharmacol. 2008 Jun 19;
Brusberg M, Ravnefjord A, Lindgreen M, Larsson H, Lindström E, Martinez V
The alpha(2)-adrenoceptor agonist, clonidine, modulates colorectal sensorimotor functions in humans and, given intrathecally, has analgesic effects in the colorectal distension (CRD) model in rats. We tested the effects of systemic clonidine on the visceral pain-related viscerosomatic and autonomic cardiovascular responses to CRD and colonic compliance in rats using clinically relevant CRD protocols. The activity of the abdominal musculature (viscerosomatic response), monitored by electromyography and intracolonic manometry, and changes in arterial blood pressure and heart rate, monitored by telemetry, were assessed simultaneously in conscious rats during CRD. Pressure-volume relationships during CRD served as a measure of colonic compliance. Clonidine (50-200 nmol/kg, p.o.) dose-dependently inhibited the viscerosomatic response to phasic, noxious CRD (12 distension at 80 mm Hg). At 200 nmol/kg clonidine also attenuated the increase in blood pressure (70+/-7% inhibition, P
Br J Pharmacol. 2008 Jul; 154(5): 1160
Villalón CM, Albarrán-Juárez JA, Lozano-Cuenca J, Pertz HH, Görnemann T, Centurión D
Alpha-2 Adrenergic Agonists Protect Against Radiocontrast-Induced Nephropathy in Mice.
Am J Physiol Renal Physiol. 2008 Jun 25;
Billings Iv FT, Chen SW, Kim M, Park SW, Song JH, Wang S, Herman J, D'Agati VD, Lee HT
Radiocontrast nephropathy (RCN) is a common clinical problem without effective therapy. Utilizing a murine model, we tested the hypothesis that alpha-2 adrenergic receptor agonists [clonidine, dexmedetomidine (dex)] protect against RCN, induced with iohexol (a nonionic low-osmolar radiocontrast). C57BL6 mice were pretreated with saline, clonidine, or dex before induction of RCN. Some mice were pretreated with yohimbine (a selective alpha-2 receptor antagonist) prior to saline, clonidine or dex administration. Alpha-2 agonist treated mice had reduced plasma creatinine, renal tubular necrosis, renal apoptosis, and renal cortical proximal tubule vacuolization 24 hrs after iohexol injection. Yohimbine reversed the protective effects of both clonidine and dex pretreatment. Injection of iohexol resulted in a rapid (~90 min.) fall of renal outer-medullary blood flow. Clonidine and dex pretreatment significantly attenuated this perfusion decrease without any changes in systemic blood pressure. To determine whether proximal tubular alpha-2 adrenergic receptors mediate the cytoprotective effects, we treated cultured human proximal tubule (HK-2) and rat pulmonary microvascular endothelial cells (RPMEC) with iohexol after vehicle, clonidine or dex pretreatment. Iohexol caused a direct dose-dependent reduction in HK-2 and RPMEC viability, but alpha-2 agonists failed to preserve the viability of both cell types. We conclude that alpha-2 adrenergic receptor agonists protect mice against RCN by preserving outer-medullary renal blood flow. As alpha-2 agonists are widely utilized during the perioperative period, our findings may have significant clinical relevance to improving outcomes following radiocontrast exposure. Key words: acute renal failure, HK-2 cells, dexmedetomidine, clonidine.
Neuropharmacology. 2008 May 18;
Dean JM, George S, Naylor AS, Mallard C, Gunn AJ, Bennet L
We have previously shown that brief alpha(2)-adrenergic receptor blockade increased neuronal injury after severe hypoxia in preterm fetal sheep. We now examine whether infusion of an alpha(2)-adrenergic receptor agonist, clonidine, is neuroprotective. Preterm fetal sheep (70% gestation) received either saline-vehicle or clonidine at either 10mug/kg/h (low-dose) or 100mug/kg/h (high-dose) from 15min until 4h after 25min of umbilical cord occlusion. Both low- and high-dose clonidine infusions after sham-occlusion were associated with transient EEG suppression but no neuronal loss. Low-dose but not high-dose clonidine infusions after umbilical cord occlusion were associated with a significant overall increase in numbers of surviving neurons after three days' recovery. High-dose clonidine was associated with transient hyperglycemia and increased numbers of delayed electrographic seizures. These results provide further evidence that alpha(2)-adrenergic receptor activation shortly after perinatal hypoxia-ischemia can promote neural recovery, but highlight the complex dose-response of exogenous therapy.
Neurosci Lett. 2008 Aug 8; 440(3): 227-31
Vibert YM, Ashraf QM, Mishra OP, Delivoria-Papadopoulos M
Previously we showed that following hypoxia there is an increase in nuclear Ca(2+)-influx and Ca(2+)/calmodulin-dependent protein kinase IV activity (CaMK IV) in the cerebral cortex of term guinea pig fetus. The present study tests the hypothesis that clonidine administration will prevent hypoxia-induced increased neuronal nuclear Ca(2+)-influx and increased CaMK IV activity, by blocking high-affinity Ca(2+)-ATPase. Studies were conducted in 18 pregnant guinea pigs at term, normoxia (Nx, n=6), hypoxia (Hx, n=6) and clonidine with Hx (Hx+Clo, n=6). The pregnant guinea pig was exposed to a decreased FiO(2) of 0.07 for 60min. Clonidine, an imidazoline inhibitor of high-affinity Ca(2+)-ATPase, was administered 12.5mug/kg IP 30min prior to hypoxia. Hypoxia was determined biochemically by ATP and phosphocreatine (PCr) levels. Nuclei were isolated and ATP-dependent (45)Ca(2+)-influx was determined. CaMK IV activity was determined by (33)P-incorporation into syntide 2 for 2min at 37 degrees C in a medium containing 50mM HEPES (pH 7.5), 2mM DTT, 40muM syntide 2, 0.2mM (33)P-ATP, 10mM magnesium acetate, 5muM PKI 5-24, 2muM PKC 19-36 inhibitor peptides, 1muM microcystine LR, 200muM sodium orthovanadate and either 1mM EGTA (for CaMK IV-independent activity) or 0.8mM CaCl(2) and 1mM calmodulin (for total activity). ATP (mumoles/gbrain) values were significantly different in the Nx (4.62+/-0.2), Hx (1.65+/-0.2, p
Med Intensiva. 2008 Feb; 32 Spec No. 1: 100-6
Alonso-Fernández MA, Estébanez-Montiel MB, Rico-Cepeda P,
The epidural analgesia is one of the most effective techniques for pain relief when it is indicated, but it can present potentially serious complications that must precociously be diagnosed and be treated. In the Critical Care setting, epidural analgesia is used for pain control after surgery or major trauma. The technique is simple, a catheter is placed into a virtual cavity, so the administered drugs are absorbed through the epidural space into nerve roots. The administration of local anesthetics, opioids or the combination of both by epidural route (administered in continuous infusion or bolus), provides better analgesia. Also the clonidine can be used. In order to diagnose and to treat suitably the possible complications (pain, urinary retention, nauseas and vomits, itching, motor block, infection, respiratory depression, hypotension) a series of safety measures must be adopted (respiratory and heart rate, blood pressure, sedation score, sensory and motor level assessment, rate of diuresis, temperature and signs of infection).
[Control strategies for difficult sedation]
Med Intensiva. 2008 Feb; 32 Spec No. 1: 31-7
Chamorro C, Romera MA,
There is a wide intra- and inter-individual variability in sedative dose requirements in mechanically ICU patients. Patient's heterogeneity, the frequent and variable organic dysfunctions, the drug interactions and the possibility of metabolite accumulation could explain this variability. However, this fact must not justify the use of excessive doses to achieve the goals of sedation. Frequently, in the absence of a specific motive, e.g. uncontrolled pain, physicians administer progressive sedative dose increases. Probably, the absence of maximum dose recommendations has originated the case's description of severe complications, sometimes mortal, or sedative toxicity, like propofol infusion syndrome. This SEMICYUC Analgesia and Sedation Work Group recommends not administering more than 4.5 mg/kg/h of propofol or 0.25 mg/kg/h of midazolam. The need to use more than these doses should force a change in the sedative or the combined administration of both. Depending on the clinical situation or the clinical patient's evolution, the use of clonidine, haloperidol or remifentanil could be better options.
Neuroimaging of mirtazapine enantiomers in humans.
Psychopharmacology (Berl). 2008 Jun 20;
Smith DF, Hansen SB, Jakobsen S, Bender D, Audrain H, Ashkanian M, Stork BS, Minuzzi L, Hall H, Rosenberg R
INTRODUCTION: Mirtazapine is a racemic antidepressant with a multireceptor profile. Previous studies have shown that the enantiomers of mirtazapine have different pharmacologic effects in the brain of laboratory animals. MATERIALS AND METHODS: In the present study, we used positron emission tomography (PET) and autoradiography to study effects of (R)- and (S)-[(11)C]mirtazapine in the human brain. Detailed brain imaging by PET using three methods of kinetic data analysis showed no reliable differences between regional binding potentials of (R)- and (S)-[(11)C]mirtazapine in healthy subjects. RESULTS: Autoradiographic studies carried out in whole hemispheres of human brain tissue showed, however, that (R)- and (S)-mirtazapine differ markedly as inhibitors of [(3)H]clonidine binding at alpha(2)-adrenoceptors. CONCLUSION: The multireceptor binding profiles of mirtazapine enantiomers, along with individual differences between subjects, may preclude PET neuroimaging from demonstrating reliable differences between the regional distribution and binding of (R)- and (S)-[(11)C]mirtazapine in the living human brain.
Anaesth Intensive Care. 2008 May; 36(3): 339-50
Peter JV, Moran JL, Pichamuthu K, Chacko B
Organophosphate poisoning is common in developing countries. The morbidity and mortality with organophosphate poisoning is relatively high despite the use of atropine as specific antidotal therapy and oximes to reactivate acetylcholinesterase. Several adjunct and alternative therapies have been explored in animal and human studies. We reviewed the literature to ascertain if there was evidence of benefit of such therapies. Adjunct and alternative therapies included treatments to reduce poison absorption by topical application of creams, enhance toxin elimination by haemoperfusion or bioremediation and neutralise the poison by scavenging free organophosphate with cholinesterase-rich human plasma. In addition, magnesium, clonidine, diazepam, N-acetyl cysteine and adenosine receptor agonists have also been used to counteract poison effects. Detailed assessment was limited by the paucity of trials on adjunct/alternative therapies. The limited evidence from the review process suggested potential benefit from the use of human plasma infusion, early initiation of haemoperfusion and intravenous magnesium, in addition to standard therapy with atropine and pralidoxime. There appeared to be no additional benefit with alkalinisation or use of glycopyrrolate instead of atropine in human trials. Diazepam administration has been advocated by military authorities if symptoms developed following exposure to organophosphate. Bioremediation, clonidine, N-acetyl cysteine and adenosine receptor agonists have been evaluated only in animal models. The impact of adjunct and alternate therapies on outcomes in human poisoning needs to be further explored before implementation as standard treatment.